Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Abstract

BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

Huntington's disease: a clinical review

“…In addition, genetic pathway analysis implicated gene pathways involved in DNA repair, mitochondrial fission and oxidoreductase activity [18]. Similarly a recent GWAS has revealed association between HD progression and a genetic variant in MSH3, a DNA repair gene, associated with CAG somatic instability [19].…”

Therapeutic effects of stem cells in rodent models of Huntington's disease: Review and electrophysiological findings

“…HD arises from an expanded repetition of the CAG codon, which codes for glutamine in the huntingtin (htt) protein. In healthy individuals, the CAG triplet repeats 10‐35 times while mutant alleles containing >36 CAG repeats predispose individuals to develop HD with time of onset depending mostly on repeat length, but also on genetic modifiers and environmental factors . The hallmark symptoms of HD include involuntary movements (chorea), cognitive deficits, and psychiatric disturbances including, prominently, depression .…”

One decade ago, one decade ahead in huntington's disease

“…Defective DNA mismatch repair, which can be contributed to by heritable genetic modifiers, is increasingly seen as the likely culprit behind such expansions. 42,43 Two individuals with the same CAG repeat length, say 42, on the standardized HD predictive genetic test performed on blood might have wildly discrepant ages of onset. Much of that difference may well be explained by the brain of the younger-onset individual containing many neurons with a true CAG of 80 or 150, whereas those of the more fortunate individual may only have expanded a little or not at all.…”